The overall objective of this project is to explore the control of myelination in the mammalian nervous system. Studies conducted to date have established that 1) the neuron and its axon regulate the myelinating behavior of the Schwann cell and oligodendrocyte, 2) a common signal for myelin formation is likely to exist both in the central and peripheral nervous systems, and 3) Schwann cells undergo atrophy and disappear after prolonged deprivation of axonal contact. Additional investigations have examined the behavior of Schwann cells during myelination and remyelination produced by toxic and traumatic insults. These observations have led to the publication of a new theory of myelination in which the neuron regulates the behavior of the myelinating cell by information exchange occuring at the apposed plasma membranes of axon and Schwann cell. Morphological and biochemical studies are proposed to test this new hypothesis by utilizing newly-developed preparations of viable, undifferentiated Schwann cells resident within the distal stumps of transected and chronically denervated tibial nerves of cats. After establishing the time-course of myelin and axon removal, tibial nerve stumps will be reinnervated by regenerating axons from freshly transected proximal stumps of peroneal nerves joined by anastomosis. The spatial-temporal appearance of myelin and myelin proteins will be correlated with the position of axons to determine how these phenomena are related. Schwann cell-enriched distal nerve stumps will also be used to prepare, characterize and study a purified fraction of Schwann cell plasma membrane. These studies will provide the baseline for future investigations which will determine the effects of neuronal factors on the properties and function of Schwann cell plasma membrane and dissect the factors responsible for instructing these cells to elaborate myelin. The overall goal of these studies is to illuminate the cause, prevention and amelioration of human demyelinating and dysmelinating diseases.